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  1. In recent years, the incidence of cancer patients has been increasing yearly. Tumor markers have become mandatory items in many human examination projects. Among so many tumor indicators, how to identify their clinical significance? Let’s learn about the clinical significance of tumor marker detection in this article. Tumor markers are a class of substances that are synthesized or released by tumor cells themselves or generated or elevated by the body's response to tumor cells. Tumor markers are present in blood, cells, tissues or body fluids, reflecting the presence and growth of tumors. Tumor markers are determined by methods such as chemistry, immunology, and genomics, for tumor diagnosis, curative effect and recurrence monitoring, and prognosis judgment Has a certain value. Tumor markers mainly include protein, sugar, enzyme and hormone tumor markers. Protein tumor markers 1.1 Alpha-fetoprotein (AFP) determination Alpha-fetoprotein is a serum glycoprotein synthesized early in the fetus. After birth, AFP synthesis is inhibited. When malignant lesions occur in liver cells or gonad embryo tissues, cells capable of synthesizing AFP restart to synthesize, resulting in a marked increase in blood AFP content. Therefore, the detection of AFP concentration has important clinical value for the diagnosis of hepatocellular carcinoma and trophoblastic malignant tumors. Reference value: <25μg/L Clinical significance: Primary liver cancer; Gonad embryo tumor; Viral hepatitis and cirrhosis (usually <300μg/L). 1.2 Carcinoembryonic Antigen (CEA) determination The CEA content in the body after birth is extremely low and it is a broad-spectrum tumor marker that can be expressed in a variety of tumors. It is mainly used to assist the diagnosis, prognosis, curative effect monitoring and tumor recurrence of malignant tumors. Reference value: <5μg/L Clinical significance: Increased CEA is mainly seen in patients with pancreatic cancer, intestinal cancer, gastric cancer, lung cancer, etc; The concentration decreases when the dynamic observation improves, and vice versa; CEA increased slightly in smoking patients. 1.3 Tissue peptide antigen (TPA) determination The level of TPA in the blood is closely related to the degree of cell division and proliferation. The higher the level of TPA in the serum, the more commonly used clinically for the auxiliary diagnosis of rapidly proliferating malignant tumors, especially for monitoring the efficacy of known tumors. Reference value: 130U/L Clinical significance: The serum TPA level of patients with malignant tumors can be significantly increased; TPA level decreases after improvement, if it rises again, it indicates relapse; The simultaneous detection of TPA and CEA is conducive to the differential diagnosis of malignant and non-malignant breast tumors. 1.4 Prostate specific antigen (PSA) determination In prostate cancer, serum PSA levels are elevated. 80% of total serum PSA (t-PSA) exists in bound form, called composite PSA (c-PSA); 20% exists in free form, called free PSA (f-PSA). t-PSA and f-PSA increased, while the ratio of f-PSA/t-PSA decreased, suggesting prostate cancer. Reference: t-PSA<4.0μg/L f-PSA<0.8μg/L f-PSA/t-PSA>0.25 Clinical significance: Prostate cancer; If the concentration of t-PSA does not decrease or rises again after prostate cancer resection, it indicates tumor metastasis or recurrence; PSA will increase after anal finger examination, prostate massage, and cystoscopy. 1.5 Squamous cell carcinoma antigen (SCC) determination SCC is a subtype of tumor-associated antigen TA-4, a glycoprotein Reference value: <1.5μg/L Clinical significance: Lung squamous cell carcinoma, cervical cancer, esophageal cancer; Some benign diseases such as psoriasis and other skin diseases, renal insufficiency, upper respiratory tract infections, etc. can also cause increased SCC concentration; Contamination of sweat, saliva and other body fluids can cause false positives. 1.6 Cytokeratin 19 fragment (CYFRA 21-1) determination Mainly distributed in tissues or organs rich in epithelial cells, such as lung, breast, bladder, intestine, etc. When these tissues become malignant, the level of CYFRA 21-1 in the blood can be seen to increase. At present, it is mainly used for differential diagnosis and prognosis evaluation of non-small cell lung cancer. Reference value <2μg/L Clinical significance: It is the preferred tumor marker for non-small cell lung cancer; In addition to lung cancer, YFRA 21-1 increased in breast cancer, bladder cancer, colorectal cancer, etc.; Other benign diseases such as pneumonia, tuberculosis, gastrointestinal diseases, etc., but their levels are slightly elevated (generally <10μg/L). Glycolipid tumor markers 2.1 Cancer Antigen 50 (CA50) It is a tumor carbohydrate antigen and has no organ specificity for tumor diagnosis. Reference value <20,000 U/L Clinical significance: Increased pancreatic cancer, gallbladder (tract) cancer, primary liver cancer, etc.; Dynamic observation of its level is of great value for the prognosis of cancer tumors and judgment of recurrence monitoring; It is valuable to distinguish benign and malignant pleural and abdominal effusions; In chronic liver disease, pancreatitis, and bile duct disease, CA50 also increases. 2.2 Cancer Antigen 724 (CA724) CA724 is a tumor-associated glycoprotein, which is a marker of gastrointestinal and ovarian cancer. Reference value<6.7μg/L Clinical significance: The increase is seen in ovarian cancer, colorectal cancer, gastric cancer, pancreatic cancer; Joint detection with CA125 can improve the detection rate of ovarian cancer; Joint detection with CEA can improve the sensitivity and specificity of gastric cancer. 2.3 Sugar chain antigen 199 (CA199) CA199 is a glycoprotein. Normal human salivary glands, prostate, pancreas, breast and other epithelial cells have a small amount of CA199. Reference value <37,000 U/L Clinical significance: The preferred tumor marker for pancreatic cancer; Can be found in acute pancreatitis, acute hepatitis, gallbladder cancer, cholangiocarcinoma, gastric cancer, colon cancer, etc.; Continuous detection is of great value to the progression of the disease, surgical efficacy, prognosis estimation and diagnosis of recurrence; Combined with CEA detection to improve the diagnosis rate of gastric cancer. To be continued in Part II…
  2. Abstract: Science has made great progress in the fight against HIV and AIDS over the last decade. And a new platform called ConvertibleCAR has shown great potential. AIDS has always been the focus of research in medical circles in various countries, because it is a disease that is relatively difficult to cure at the current medical level, and it also damages the human immune system greatly, and thus is easy to cause complications and eventually lead to death. A study by the Gladstone Institute shows that a new technology based on CAR-T cell immunotherapy shows great hope in multiple therapeutic areas, especially in the fight against HIV. This new technology is called ConvertibleCAR®, and related research results were published in Cell on October 24, 2019. The potential pool of HIV is the main obstacle to cure AIDS, and Dr. Warner C. Greene, who is the director of the Center for HIV Cure Research in Gladstone Institute as well as the corresponding author of the paper, has been hoping to target it and clear the virus. Conventional CAR-T technology is required to transform an immune cell form, that is, cytotoxic T cells, to express antibodies on the surface. The antibody part allows cytotoxic T cells to reside in target cells (such as leukemia cells) and thus to attack and destroy them. Dr. Eytan Herzig of Gladstone Institute, the first author of the paper, said: "The disadvantage of traditional CAR-T is that they are designed to target a single molecule on cancer cells and once injected, they cannot be controlled. In contrast, ConvertibleCAR technology makes it possible to combine cytotoxic "killer" T cells with any number of antibodies. This is essential for resistance to pathogens such as HIV, because there are hundreds of different variants of HIV. In this paper, scientists have overcome shortcomings by separating targeted antibodies from cytotoxic killer cells. The modified NKG2D receptor can turn T cells into an effective killer only if it binds to its partner, which is a protein called MIC-A. The researchers trimmed and modified MIC-A so that it can specifically bind to the NKG2D receptor. Then, they fused it to the base of the targeted antibody and created the so-called MicAbody®. In this way, targeting MicAbody can be tightly combined with ConvertibleCAR-T cells. To eliminate the potential pool of HIV, researchers have been testing a wide range of Broadly Neutralizing HIV-1 Antibodies (bNAb). Herzig explained: “They are called broadly neutralizing antibodies because they can neutralize a large number of strains of virus.” But bNAb alone is not enough to kill HIV-infected cells. They need the help of killer T cells, and in HIV-infected patients, the problem is that the killer T cells have been exhausted, or the potential reservoir contains viruses that are resistant to these cells. Herzig and Greene believe that by combining bNAb and ConvertibleCAR-T cells, they may obtain the required lethality. Herzig and Greene tested whether the ConvertibleCAR-Mic-bNAb platform could attack the latent reservoir in the blood of HIV-infected people on antiretroviral therapy (ART). The results prove that the transformable CAR-T cells specifically bind to Mic-bNAbs to kill the infected CD4 T cells, but not the uninfected cells. It was also found that within 48 hours after exposure, more than half of the activated, HIV-expressing cells had been eliminated. Dr. Eytan Herzig will explain more about this technology in the upcoming webinar held at 3:00 p.m. EDT on June 4th, 2020. The webinar entitled “ConvertibleCAR-T, a highly adaptable CAR-T platform to fight HIV” is sponsored by Creative Biolabs, a leading biotech manufacturer focusing on one-stop CAR-T/NK Cell therapy development service. One thing interesting about CAR-T cells is that they first appeared in the late 1990s to fight against HIV, but failed. And then traditional CAR-T cells have achieved great success in relieving blood cancers such as lymphoma and childhood leukemia. Now, it comes back to HIV treatment with greater lethality and may even be the key method to overcome AIDS.
  3. Creative Biolabs has provided financial support for the young and talented college student in form of yearly scholarship for 4 years in a row and will keep it as a convention, with the aim to help them continue their study into the science-related fields. May—New York, USA Affected by the COVID-19, most American universities have switched their teaching mode from face-to-face to distance learning, hoping to proceed with the education plan of this semester to minimize the influence on graduation. At Creative Biolabs there is a group of Ph.D. level scientists who have been exploring in the field of biology, biochemistry, chemistry and molecular biology. With the professional theoretical framework constructed in their specialties in university for years, plus practical experience gained in hundreds of projects, the experts deeply realize the longer they get involved in their fields, the more they love. Therefore, they firmly believe that encouraging the younger generation to discover in their interested scientific fields is of vital importance, which is also the original intention to set up the Creative Biolabs Scholarship Program. The scholarship application procedure is just like those of American universities that students should submit an application form, transcripts, recommendation letter (from a lecturer, school counselor or community leader), an essay, or a PPT over certain topics. Previously, reference letter was not a must but an additional material since the scholarship committee mainly evaluate the academic ability of candidates according to their academic records and propositional essays. This year, application materials from any one of the candidates without a reference letter with the designated format will be considered incomplete, and result in disqualification automatically. "We think the comprehensive ability of a candidate is also important, " said the head of the Scholarship Committee at Creative Biolabs, "the evaluation from others can be a good reference." Another significant material other than the academic transcript is the essay, or the PowerPoint document that must be totally original and grammatically right, reflecting the real insight of students in their fields. The topics include: l Overview on Clinical Applications of Oncolytic Viruses l Novel Gene Delivery Systems for Gene Therapy l Applications of Protac Technology in Disease Treatment l Overview on Clinical Applications of Stem Cell Therapy Considering the current situation that many students may have limited access to library resources or their referrers, Creative Biolabs modifies the submission deadline of all applications. "Not like last year, we extend the application to September 15," said the head of the Scholarship Committee, "to ensure the students have enough time to finish their essays, or find a referrer." As a leading custom service provider specialized in the field of antibody production and engineering, Creative Biolabs is always happy to support young and ambitious talents in the medical and science-related field. More details about the application procedures and requirements can be accessed at https://www.creative-biolabs.com/scholarship-program.html. Company profile: Creative Biolabs is a US based biotechnology company with specialties in antibody discovery, engineering and providing relative custom solutions.
  4. As the most extensive renewable energy (23,000 TW/year) in nature, how to realize its efficient and reasonable development and utilization has always been a research hotspot for scientific researchers. From the current development stage, the utilization of solar energy mainly focuses on three aspects: solar power system, solar thermal system and solar fuel system. However, the intermittent problem of regional light source caused by Earth rotation greatly limits the continuous conversion of solar energy to other energy sources, so that it cannot meet the continuous energy demand in daily production and life. In response to the problem, scientists put forward the corresponding energy reserve strategy. By combining the photoelectrochemical system with the secondary cell or liquid flow cell system, the conversion and storage of solar energy are realized, and the energy supply and demand caused by the intermittent light source are effectively solved. However, the multi-system connection has the disadvantages of complex system, high cost and serious energy transmission loss. Therefore, how to design the integrated solar energy storage system rationally has become the next research problem that researchers need to solve. Recently, Shaojun Dong’s team at Changchun Institute of Applied Chemistry, Chinese Academy of Sciences realized the continuous transformation and storage of solar energy under an integrated system by constructing a bio-photoelectrochemical model based on water/oxygen circulation, providing a new research idea for the efficient use of renewable energy. The team designed the bio-photochemical system to use polypyrrole solid-state capacitive electrodes as energy storage modules to make the energy storage process safer and easier. In the process of solar energy storage, the water/oxygen molecules in the system can spontaneously form a cycle without the participation of additional sacrifice reagents and other redox pairs, which greatly improves the safety of the equipment and reduces the cost. In addition, the modular and integrated structural design of this system enables it to be adjusted and optimized according to different circumstances and better meet the practical application needs of many aspects. Experimental data analysis showed that the conceptual model obtained maximum power density outputs of 0.34 ± 0.01 and 0.19 ± 0.02 mWcm-2 under light and dark field conditions, respectively, and showed stable solar accumulator cycle performance. By changing the capacitance of the energy storage module (polypyrrole capacitive electrode), the charge/discharge time can be effectively regulated. In this research work, the construction of bio-photoelectrochemical model of water/oxygen cycle promotes the development of cross-integration among photoelectrochemical system, bioelectrochemical system and capacitor system on the one hand, and also provides certain guiding significance for the future research and development of green rechargeable devices on the other hand. The results were recently published in the Journal of the American Chemical Society, (2019, 141, 16416-16421), and were supported by the National Natural Science Foundation of China and the Ministry of Science and Technology of China. About Author As a biotechnology company, Lifeasible is specialized in agricultural science, offering a wide variety of agro-related services and products for environmental and energy solutions. Our plant breeding and culture services support increasingly stringent safety and quality standards in the agricultural industry. Relying on our revolutionary techniques, various molecular breeding services and molecular diagnostic methods are offered for a wider range of agriculture-related sectors.
  5. According to reports, the rapid spread of COVID-19 has led to a surge in the number of suspected infections and close contacts. The early detection of the virus can not only enable the infected person to be treated in time and reduce the risk of death, but also can effectively control the source of the infection and cut off the transmission route through isolation. Generally, there are two detection strategies for infectious diseases: nucleic acid detection and immunological detection. Nucleic acid detection is the detection of viral RNA genome, including gene sequencing, quantitative real-time PCR, digital droplet PCR, gene chip and Loop-Mediated isothermal amplification. Immunological detection is the detection of specific antibodies produced by viral antigens or by human immune responses, including immunochromatographic strips, enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA). The following compounds provieded by BOC Sciences can be used in the production of COVID-19 test kits: Guanidine thiocyanate Guanidine thiocyanate is a colorless crystal or white powder, soluble in water. It is an anticoupling agent and a strong protein denaturation agent, which can dissolve proteins, and quickly separate the nucleic acid from nuclear proteins. The combination of guanidine thiocyanate and mercaptoethanol is able to inhibit the activity of RNase. The combined action of guanidine thiocyanate and sodium dodecyl sarcosine can denature proteins and release RNA. Guanidine hydrochloride Guanidine hydrochloride, white or yellowish in color, is used as a protein denaturator. As a strong denaturation agent for extracting total RNA from cells, guanidine hydrochloride solution can dissolve proteins, destroy the secondary structure of nucleoproteins dissociated from nucleic acids. In addition, guanidine hydrochloride and other reducing agents can inactivate RNA enzymes. Using dicyandiamide and ammonium salt (ammonium chloride) as raw materials, crude guanidine hydrochloride products can be obtained at 170-230℃. Tris(hydroxymethyl)aminomethane Tris(hydroxymethyl)aminomethane is a common buffer in molecular biology and cell culture. Tris buffer has a high buffering capacity, high solubility in water, and is inert to many enzyme reactions, which makes Tris a very satisfying buffer for many biochemical purposes. It is generally used to stabilize the pH of reaction system and has a strong buffering capacity between pH 7.5 and pH 9.0. Tris-HCl buffer system can also be used to stabilize the pH value in the gel. Tris buffer is widely used as a solvent for nucleic acids and proteins. Due to the low ionic strength, Tris buffer can also be used for the formation of intermediate fibers in nematodes. "TE buffer" prepared by adding EDTA into Tris hydrochloric acid buffer can be used for DNA stabilization and storage. HEPES HEPES buffer, mainly composed of 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, is a non-ionic amphoteric buffer with good buffering capacity in the pH range of 7.2-7.4. Its greatest advantage is that it can maintain a relatively constant pH value in open culture or cell observation. Under these conditions, the cap of the cell culture bottle should be tightened to prevent the small amount of carbonate needed in the culture solution from being dispersed into the air. HEPES is difficult to dissolve in any other solvents, but it is readily dissolves in water, and does not precipitate with polyvalent metal ions. In addition, most natural factors such as temperature, concentration, medium salinity, and ion composition do not affect the dissociation of HEPES, so the stability of HEPES is excellent. DTT DTT, short for DL-dithiothreitol, is used to block the formation of intramolecular or intermolecular disulfide bonds between cysteines in proteins. The effect of DTT on proteins is that it can reduce disulfide bonds in proteins. One of the uses of DTT is as a reductant for sulfhydrylated DNA. Sulfur atoms at the ends of sulfhydrylation DNA tend to form dimers in solution, especially in the presence of oxygen. This dimerization greatly reduces the efficiency of some coupling experiments, such as DNA fixation in biosensors.
  6. 3.2 The immunoregulatory effect of mesenchymal stem cells on B cells B cells are pluripotent stem cells derived from bone marrow. With the stimulation of antigens and T cells, they proliferate in large quantities and further differentiate and develop into plasma cells capable of secreting antibodies. Mesenchymal stem cells have a certain inhibitory effect on the proliferation and differentiation of B cells. Mesenchymal stem cells can induce B cell proliferation and differentiation through cell contact. These conclusions may be related to the cell purification method, culture environment and detection time point, etc., and further research is needed. In addition, the functions of B cells secreting antibodies and expressing chemokine receptors CXCR4, CXCR5, and CCR7 are inhibited by mesenchymal stem cells, while the secretion of B cell costimulatory molecules and cytokines is not affected by mesenchymal stem cells. The effect of mesenchymal stem cells on B cells is achieved through cell contact, and PD-1 / PDL-1 pathway is an important way for mesenchymal stem cells to inhibit B cells. Studies have shown that PD-1 can dephosphorylate some key signal transducers of BCR signaling by accumulating phosphatase, thereby hindering BCR signaling and inhibiting B cell activation. In addition, there are studies suggesting that T cells play an important role in the immune regulation of mesenchymal stem cells to B cells. Mesenchymal stem cells inhibit the proliferation and differentiation of B cells, but require the interaction between T cells and mesenchymal stem cells. In addition to the key role of cell contact, mesenchymal stem cells regulate B cell function. Soluble cytokines also play a role that cannot be ignored. The study found that mesenchymal stem cells secrete CCL2, and achieve immune regulation of B cells by suppressing transcriptional activator protein 3 and inducing the production of paired box protein 5 (PAX5). In the mesenchymal stem cell co-culture system, the m RNA expression of Blimp-1 is significantly reduced, and the m RNA expression of PAX-5 is increased. Inhibiting the expression of Blimp-1 and promoting the expression of PAX-5 can inhibit the proliferation and differentiation of B cells. 3.3 The immunomodulatory effect of mesenchymal stem cells on NK cells NK cells are short for natural killer cells. It is different from T cells and B cells; it does not require specific antibodies to participate in the killing of target cells or antigen-specific sensitization. The main role of NK cells in the innate immunity of the human body is to distinguish normal and abnormal cells by recognizing the ligands of corresponding activated receptors and inhibitory receptors on target cells. They also play a role in immune surveillance. Mesenchymal stem cells can inhibit the proliferation and function of NK cells. NK cells are stimulated by activated cytokines, resulting in high expression of NK cell surface activated receptors NKp30, NKG2D, NKp44, CD69. The activated receptors on the surface of these cells are closely related to the function of NK cells. When NK cells and mesenchymal stem cells are co-cultured, the expressions of NK cell activation receptors NKp30 and NKG2D will be reduced, and NKp44 will not be expressed. Therefore, mesenchymal stem cells inhibit the cytotoxicity of NK cells by inhibiting the expression of NK cell activation receptors. FN-γ plays a key role in the inhibition of mesenchymal stem cells on NK cells. The sensitivity of mesenchymal stem cells to NK cytotoxicity can be reduced by the presence of IFN-γ. The role of IFN-γ may be to induce mesenchymal stem cells to overexpress HLA molecules and interact with the inhibitory receptors of NK cells, thereby inhibiting the cytotoxicity of NK cells. Indoleamine 2,3-dioxygenase, prostaglandin E2, HLA-G play a major role in the inhibition of mesenchymal stem cells on NK cells. The HLA-G receptor is expressed on the surface of a leukocyte called LILRB, and can be expressed on the surface of T, B, and NK cells. The interaction of HLA-G / LILRB2 blocks the MEK / ERK signaling pathway and inhibits the cytotoxicity of NK cells. Adding indoleamine 2,3-dioxygenase or prostaglandin E2 to the mixed culture of mesenchymal stem cells and NK cells can restore the proliferation of NK cells to a certain extent. In the presence of IFN-γ and tumor necrosis factor alpha, mesenchymal stem cells interact with NK cells, mesenchymal stem cells secrete prostaglandin E2, and subsequently prostaglandin E2 can promote indoleamine 2,3-dioxygenase synthesis. In addition, the inhibitory effect of mesenchymal stem cells on NK cells is concentration-dependent. As the ratio of NK / mesenchymal stem cells increases, the inhibitory effect of mesenchymal stem cells on NK cells weakens. 3.4 The immunomodulatory effect of mesenchymal stem cells on dendritic cells Dendritic cells are important antigen-presenting cells, derived from pluripotent hematopoietic stem cells. Immature dendritic cells have extremely strong antigen uptake, processing and processing capabilities. After ingesting the antigen or being stimulated, immature dendritic cells (CD14-, CD1a +) can differentiate into mature dendritic cells (CD80 +, CD83 +, CD86 +), and during this process, their antigen uptake and processing capacity will be significantly reduced, and their ability to present antigens and stimulate immune responses will be enhanced. Dendritic cells are presented to the corresponding CD8 + T cells and CD4 + T cells through the abundant antigen peptide-MHC class Ⅰ molecular complex and antigen peptide-MHC class Ⅱ molecular complex on their membrane surface, thereby activating T cell response and allowing T cells provide costimulatory molecules to fully activate T cells. Mesenchymal stem cells can inhibit the differentiation of pluripotent hematopoietic stem cells into dendritic cells and the maturation of dendritic cells. Under the stimulation of granulocyte-macrophage stimulating factor / interleukin 4, the co-culture of mesenchymal stem cells and monocytes reduced the expression of CD1a and the high expression of CD14, indicating that the differentiation of dendritic cells was inhibited. In addition, under the stimulation of lipopolysaccharide, mesenchymal stem cells were co-cultured with dendritic cells, the expression of maturation marker CD83 of dendritic cells was decreased, the expression of costimulatory molecules CD80 and CD86 on the surface of dendritic cells was decreased, and the expression of costimulatory molecules CD80 and CD86 on the surface of DR was decreased, the expression of antigen presentation molecule HLA-DR was decreased, and the secretion of interleukin 2 was decreased, indicating that mesenchymal stem cells inhibited the maturation of dendritic cell. When the ratio of mesenchymal stem cells / monocytes is high (1:10), the inhibitory effect of mesenchymal stem cells on the differentiation of monocytes into dendritic cells can be completely achieved by soluble factors. When the ratio of mesenchymal stem cells / monocytes is low (1:20 or 1:40), mesenchymal stem cells exert their inhibitory effect mainly through cell contact. Mesenchymal stem cells can inhibit the differentiation of CD34 + -derived CD14 + precursor cells and monocytes into CD1a + dendritic cells, and inhibit the maturation and function of dendritic cells. The addition of macrophage colony stimulating factor and interleukin 6 antibody can reduce the expression of CD14, but cannot restore the expression of CD1a, suggesting that macrophage colony stimulating factor and interleukin 6 are involved in the suppression of mesenchymal stem cells. The inhibitory effect of mesenchymal stem cells on the differentiation and maturation of dendritic cells indirectly leads to the inhibition of T cell activation, thereby suppressing the adaptive immune response. Mesenchymal stem cells have an inhibitory effect on dendritic cells through cell contact and soluble factors. This inhibitory effect may also involve macrophage colony stimulating factor, interleukin 6 and prostaglandin E2, and its specific mechanism needs further study. At present, there are many clinical trials on the immune regulation of mesenchymal stem cells, and different mesenchymal stem cell isolation methods and different mesenchymal stem cell sources have different effects on the immune regulation of mesenchymal stem cells. Mesenchymal stem cells play an immunoregulatory role in the microenvironment, and different microenvironments also have different effects on their immune regulation. References [1] Che N, Li X, Zhang L, et al. Impaired B cell inhibition by lupus bone marrow mesenchymal stem cells is caused by reduced CCL2 expression. J Immunol.2014;193(10):5306-5314. [2] Ribeiro A, Laranjeira P, Mendes S, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther.2013;4(5):125. [3] Nekanti U, Dastidar S, Venugopal P, et al. Increased proliferation and analysis of differential gene expression in human Wharton's jelly-derived mesenchymal stromal cells under hypoxia[J]. International Journal of Biological Sciences, 2010, 6 (5) :499-512. [4] Boxall SA, Jones E. Markers for characterization of bone marrow multipotential stromal cells[J]. Stem Cells International, 2012, 2012, 975871.
  7. Potential therapies for SARS-CoV-2 can be divided into two categories: one directly targets the novel coronavirus, and the other is human-oriented. Viruses must enter the host cell to replicate in order to function. Therefore, antiviral drugs can be designed for a series of targets in the process of virus interaction with cell receptors, gene replication, transcription and translation when the virus invades host cells and completes its life cycle. In addition to the above drug research and development against the virus, we can also take the human body as a guide to find therapeutic drugs for the immune response caused by the virus. In the early stage of viral infection, the human body's own immunity can be appropriately improved/activated by the activation of interferon or innate immune receptors to fight the virus. For severely advanced/immune hyperactive patients, since patients are attacked by their own immune system, they can consider using immunosuppressive drugs or mechanisms to adjust. In addition, it can also be treated against the mechanism/target where the host and the pathogen interact with each other. Currently, the main treatment methods for the disease include small molecule drugs, biomacromolecule drugs, gene therapy, cell therapy, traditional Chinese medicine therapy, and medical devices. The potential applications of them in the treatment of SARS-CoV-2 are as follows. Chemical small-molecule drugs: Small-molecule drugs are currently one of the types of drugs that are expected to be used for the treatment of SARS-CoV-2. There are now multiple small-molecule drugs in clinical trials, and their effectiveness and safety against the coronavirus needs to be further verified. Biomacromolecule drugs: These drugs have high specificity and strong continuity and compliance in the body, but their production cost is high, and because they only act on the cell membrane and outside the membrane and cannot enter the cell, so the target is limited. At present, no specific antibodies have been found to conduct clinical trials in the research of the coronavirus. At the same time, by extracting neutralizing antibodies from the plasma of some recovered covid-19 patients with sufficient concentration of effective antibodies, the potentially harmful components can be removed to treat critically ill patients, but it is unlikely to be promoted on a large scale. Gene therapy: A disease treatment method developed in recent years. It usually uses transgenic methods to make up for missing functional genes or strengthen gene functions. A variety of methods have been developed, such as precise gene editing. However, there is no gene therapy for the coronavirus. This method is generally for chronic, long-term viral infections, such as gene editing of human cells, so that the pathogens lose the ability to infect the cells, or suppress the virus gene expression through RNA interference. Cell therapy: Also a disease treatment method developed in recent years. One of the cell treatment methods is to supplement and replace the missing cells, such as the use of stem cells; one is to regulate the body's immunity by cytokines secreted by the transplanted cells, and this way is not to supplement or replace the cells, and then the transplanted cells will disappear; the other is that the transplanted cells can target and attack specific harmful cells, such as the specific recognition and removal of cancer cells by CAR-T cells. Cell therapy has been studied in the treatment of the SARS-CoV-2, such as the use of mesenchymal stem cells for immune regulation. In the future, we can also consider using specific stem cells for tissue repair and regeneration; organoids derived from stem cells can be used for disease modeling and drug screening. Medical device treatment: In addition to drug treatment, respiratory support treatments that rely on medical devices, such as oxygen therapy, invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and circulation support, also played an important role in the treatment of severe and critically ill patients with COVID-19. Traditional Chinese medicine treatment: SARS-CoV-2 belongs to the category of "epidemic" diseases of traditional Chinese medicine. Its research idea is different from Western medicine. It does not aim at a specific target but cures the disease in a systematic way. Through in-depth observation and treatment of patients, on the basis of summarizing and analyzing the diagnosis and treatment schemes of traditional Chinese medicine across the country, combing and screening the treatment experience and effective prescriptions in various regions, it is necessary to judge its effectiveness and safety through rigorous clinical trials.
  8. RNA interference (RNAi) is a revolutionary discovery in genetic research. RNAi can specifically silence endogenous or exogenous target genes, which is a rapidly developing gene control technology with broad application prospects. Since Tuchl et al. found in 2001 that artificially synthesized double-stranded small interfering RNA (siRNA) can efficiently silence the expression of target genes in mammalian cells, the life science field has set off a wave of basic and applied research on siRNA. With the gene silencing mechanism, significant progress has been made in the development of siRNA drugs to treat diseases. In August 2018, the world’s first siRNA drug, Onpattro (Patisiran) was approved by the FDA for the treatment of patients with polyneuropathy caused by hATTR. Onpattro is the world's first drug developed based on the Nobel Prize achievement RNA interference technology. In 1998, Andrew Fire and Craig Mello revealed the RNAi phenomenon for the first time in C. elegans, and won the Nobel Prize in Physiology in 2006 for this discovery. The approval of the first siRNA drug in 2018 takes 20 years. Onpattro's approval marks a major breakthrough in the field of RNAi medicines, and small nucleic acid medicines are finally dawning. According to statistics, among disease-related proteins in the human body, more than 80% of the proteins cannot be targeted by current conventional small molecule drugs and biological macromolecular preparations, and are non-drugable proteins. Gene therapy aimed at treating diseases through gene expression, silencing and other functions is considered by the industry as the third generation of therapeutic drugs after chemical small molecule drugs and biological macromolecular drugs. This kind of therapy achieves the treatment of diseases at the genetic level, not restricted by non-drugable protein. As the most mainstream type of RNA drugs in gene therapy, siRNA drugs are used to treat diseases from the level of mRNA. Compared with chemical small molecular drugs and biological macromolecular drugs, they have a higher efficiency at the protein level. In 2004, Bevasiranib, an siRNA drug developed by Opko in the United States, launched a clinical trial for the treatment of wet age-related macular degeneration. This is the first clinical trial related to siRNA in the world. Subsequently, many global pharmaceutical giants, including Pfizer, Sanofi, Roche, and Merck, joined the development queue of siRNA drugs. Unfortunately, the development of the Bevasiranib project has failed in phase III due to poor clinical results, and other latecomers have not been spared. The reason is that the poor targeting, off-target effects and stability of RNAi drugs are the most important constraints that affect their efficacy. Many factors have led to the efficacy of these drugs being far less than expected, but also accompanied by serious insurmountable medication side effect. From the perspective of technical requirements, siRNA after intravenous injection is easily degraded by nucleases, has high renal clearance, poor cell uptake efficiency, and clinical application is limited. The success of siRNA drugs depends on the development of drug delivery system technology, especially the ability to delivery carrier technology that transports RNAi safely and efficiently to specific therapeutic targets in the body. As the world's first approved siRNA drug, Patisiran adopts the LNP drug delivery system to encapsulate RNAi drugs in liposomes, which can be administered by intravenous injection. The liposome coating greatly improves the stability of the drug and the targeting of liver tissue can ensure that the siRNA will not be filtered by the kidney and will be gradually taken up by the target cells of the liver tissue during the blood circulation. This is the key to Patissiran to overcome the above major constraints and get approved for marketing.
  9. Proteolysis targeting chimeras (PROTAC) Proteolysis targeting chimeras (PROTAC) is currently a very hot drug development technology and is considered by the industry as a star of small molecule drug development. One end of this type of bifunctional small molecule is a ligand that targets the target protein, and the other end is a ligand that binds to E3 ubiquitin ligase, which is then connected by a linker of a certain length. In this way, the target protein and E3 ubiquitin ligase can be brought closer together, so that the target protein is labeled with ubiquitin, and then degraded by the ubiquitin-proteasome pathway. The main advantages are as follows: Targeted degradation "non-drugable targets", such as KRAS, STAT3, etc.; Overcome tumor drug resistance; Extend the action time; PROTACcan affect protein enzyme function and regulation Non-enzymatic function. The development history of PROTAC The technology has been developing for 20 years. Proteinix researchers submitted a patent application for the degradation of specific proteins using small molecule compounds based on the ubiquitin mechanism in 1999. Two years later, Dr. CraigCrews and Dr. Raymond Deshaies designed a series of bifunctional small molecules based on peptide compounds to induce the degradation of methionine peptidase 2 (MetAP-2), and formally proposed the concept of PROTAC. However, because these compounds, which are based on large and bulky peptides, are difficult to connect to cells, the first generation of PROTACs failed. Until 2008, the Crews team designed the second-generation PROTACs that can be used to degrade the androgen receptor (AR) based on E3's ubiquitin protein ligase MDM2. In 2015, the Crews team designed a new generation of PROTACs based on the new E3 ubiquitin ligase VHL and CRBN ligands to reduce the level of multiple proteins by more than 90%. It was also this year that James Bradner, head of research and development at Novartis, published a new generation of PROTAC molecules based on thalidomide analogues in Science, thus detonating the entire field. In 2013, Crews established Arvinas, the world's first company to develop drugs using PROTAC technology. What is optimistic about this technology is that the world's first PROTAC drug ARV-110 developed by the company is intended to be used for the treatment of castration-resistant prostate cancer. It has entered the stage of clinical phase I research. The initial data of clinical phase I indicate that ARV -110 has good oral availability and good safety and tolerability. About ARV-110 ARV-110 is the world's first oral bioavailable PRAOTC small molecule drug, which selectively targets the degradation of androgen receptor (AR). In May 2019, ARV-110 received FDA fast-track approval, mainly for the treatment of metastatic trend-resistant prostate cancer (mCRPC). In developed Europe and the United States, mCRPC is the second most frequent malignant tumor among men, and it has also been a difficult treatment and a hot spot in clinical research in the field of prostate cancer. At present, the first-line treatment drugs mainly targeting the androgen receptor target (AR) include abiraterone and enzalutamide. In addition, in March 2020, the American Society of Clinical Oncology Genitourinary System Cancer Symposium (ASCO-GU2020) discussed that for patients with mCRPC carrying DNA damage repair mutations (DDM), Abiraterone is more effective than Zalu for first-line treatment. Amine has a tendency to have better therapeutic effects. The use of androgen receptor targeting (ARAT) drugs (Abiraterone or Enzalutamide) for first-line treatment of mCRPC patients will result in more survival benefits for patients, especially for intraductal carcinoma of the prostate (IDC-P). However, for patients with AR gene or gene enhancer amplification or AR point mutations, the current first-line treatment drugs are less effective, and 15-25% of patients do not respond to second-generation hormone therapy such as abiraterone and enzalutamide. Most patients with responsiveness will eventually develop severe drug resistance, leading to a poor prognosis. The PRAOTC molecule ARV-110 targeting androgen receptor degradation currently shows excellent activity in clinical models of AR mutation and overexpression. The mechanism of ARV-110 To overcome these challenges and improve current treatment options, ARV-110 uses the ubiquitin-protease system to degrade the AR protein that plays a key role in the development of prostate cancer. It is different from traditional inhibitors and does not need to be inhibited by "occupying" receptors. In addition, the PROTAC drug can also work repeatedly to degrade the newly transcribed target protein, so it can overcome the increase in target protein expression and mutations in the target protein. The specific molecular structure has not yet been announced. Related preclinical studies In preclinical studies, ARV-110 has shown promising activity as a targeted degradation agent for AR. In a model sensitive to enzalutamide, ARV-110 showed a reduction in prostate-specific antigen (PSA) similar to enzalutamide, and the dose was lower. In the model of enzalutamide resistance, ARV-110 can significantly inhibit tumor growth. Clinical trials On May 29, 2019, the FDA approved a phase I, open-label, dose-escalation clinical phase I trial to evaluate ARV in patients with metastatic castration-resistant prostate cancer who had previously received at least two systemic therapies -110 safety, tolerability, pharmacokinetics and pharmacodynamics. The trial is expected to enroll 36 patients, 18 years of age or older and have received at least two approved CRPC systemic therapies (at least one must be abiraterone or enzalutamide). Patients with progressive mCRPC must undergo ADT (prostate cancer androgen deprivation therapy) or orchiectomy. The latest clinical data On May 13, 2020, the latest safety-related data and early efficacy data of the Phase I clinical trial (NCT03888612) were published in the abstract of the American Society of Clinical Oncology (ASCO). To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARV-110, mCRPC patients who have previously received at least 2 treatment regimens (including enzalutamide and/or abiraterone) are taken orally once daily ARV-110. Endpoints include dose-limiting toxicity (DLT), adverse events (AEs), pharmacokinetics (PK), biomarkers (eg AR mutation analysis), RECIST (evaluation criteria for the efficacy of solid tumors) and PSA (prostate specific antigen) responses. As of January 2020, there were 18 patients participating in the trial. The doses were divided into 4 groups, namely 35 mg (3 cases), 70 mg (4 cases), 140 mg (8 cases), and 280 mg (3 cases). Among them, 12 patients were previously treated with enzalutamide and abiraterone; 14 patients had received chemotherapy. One of the 18 patients had grade 4 (Gr) dose-limiting toxicity (DLT, 280 mg) while taking the cholesterol drug Rosuvastatin (DLT, 280 mg) and hepatic transaminase AST/ALT increased, followed by acute renal failure. The second patient had grade 3 (Gr) dose-limiting toxicity when taking the cholesterol drug rosuvastatin and hepatic transaminase AST/ALT also increased. After stopping rosuvastatin, ARV-110 treatment can be continued. In these two patients, in view of the significant increase in rosuvastatin plasma concentration at the same time as AST/ALT, the use of rosuvastatin and ARV-110 should be banned at the same time. In addition, there are no other relevant grade 3/4 adverse events (AE) reported. 15 patients underwent PSA response assessment (not including 1 patient who stopped treatment due to disease progression and 2 patients who had just started treatment). Eight of these patients had an initial dose of 140 mg. Two patients in the 140 mg dose group had a PSA reduction of greater than 50%. The two groups had previously received enzalutamide and abiraterone, chemotherapy, bicalutamide and radium 223, and other treatment options. One patient had 2 AR mutations known to cause enzalutamide resistance. Another patient also received an unconfirmed partial RECIST response (confirmation test to be determined). At the time of data cut-off, patients undergoing longer cycles (8 weeks and more than 21 weeks) of treatment trials are still ongoing. The latest clinical trial data shows that ARV-110 has acceptable safety. The maximum tolerated dose (MTD) has not been established and the phase 2 recommended dose (RP2D) is still being tested. In addition, for patients receiving enzalutamide/abiraterone treatment, ARV-110 has shown anti-tumor activity, of which 2 patients have been confirmed by PSA response, and 1 of them is related to tumor reduction.
  10. C5 is the first complement molecule that forms the membrane attack complex (MAC). C5 is composed of ax and β chains connected by disulfide bonds. alpha chain is 115 KDa and the β chain is 75 KDa. There is no intra-chain thioester bond molecular weight of 190 KDa. The 74-75 arginine-leucine bond near the N-terminus is where C5 convertase acts. Under the action of C5 convertase, a small fragment C5a with a molecular weight of 11 KDa was cleaved into the liquid phase. C5a is the most potent mediator of complement lysis fragments with allergic toxins." Current studies indicate that high concentrations of C5a may reduce tumors by increasing Gr4 CD11b bone marrow cells in peripheral blood. Surface CD4, CD8T cells promote the formation of tumor blood vessels and inhibit apoptosis to promote tumor growth. Low concentrations of C5a can inhibit tumor growth by stimulating immune cells and blocking the cell cycle, or low concentrations of C5a can stimulate M1 phagocytes and NK cells to tumor. On the surface, both M1 phagocytes and NK cells have a certain anti-tumor effect and thus exhibit an indirect anti-tumor effect. Therefore, the tumor-related value of C5a has a certain concentration dependence. The concentration of C5a on the tumor surface may be the key to inhibition or promotion its performance. In addition, it has also been reported that the C5a receptor expressed on the surface of the tumor can significantly enhance the tumor's invasiveness, and the cytokines stimulated by C5a such as hepatocyte growth factor can also enhance the tumor's invasiveness. At present, the research on the relationship between C5 and parenchymal organ fibrosis has been widely carried out. Boor et al.6 found that the mechanism of C5 involvement in parenchymal organ fibrosis may be related to the C5a receptor expressed on the cell surface, C5a stimulation-related cytokines and changes in parenchyma. Organ hemodynamics is related, on the other hand, there are studies that C5a has a biological relationship with liver regeneration. The three sites included in this study are all SNPs that are currently confirmed to be functional in the C5 gene. The rs17611 allele A was mostly severe cirrhosis patients and the rs2300929 allele C was mild cirrhosis patients. The C5 gene polymorphism has a clear relationship with the cirrhosis process. In another aspect, studies have indicated that the C5 serum concentration of carriers of rs17611 allele A and rs2300929 allele T is significantly higher than that of non-carriers. There is no relationship between C5 activity and C5 gene polymorphism, which suggests that there may be other factors affecting C5 activity. The gene polymorphism at rs25681 has also been shown to be associated with susceptibility to periodontitis. As in previous studies, this study also verified that there was a linkage disequilibrium among the three sites included, so that haplotype analysis was performed to obtain more genetic specificity than unit site analysis. The results of this study show that the risk of HCC is significantly increased in those who carry the rs17611 allele G, rs25681 allele C and rs2300929 allele C, and the haplotype rs17611G-rs25681C-s2300929C can increase the risk of HCC. However, study showed that the C5 serum concentrations of carriers of rs17611 allele G and rs2300929 allele C were significantly lower than those of non-carriers, and low concentrations of C5a showed a certain anti-tumor growth effect, which is obvious different from this study. Different clinical phenotypes due to different diseases in different populations have been confirmed in a number of clinical genetic studies. In addition, Halangk et al. did not find C5 gene polymorphism and the degree of cirrhosis is related. This also shows that genetic polymorphism and clinical phenotype are not the same-there are many influencing factors in the corresponding relationship. How the C5 gene polymorphism affects its serum concentration is still unclear, and the tumor-related role of C5a is still unknown. Since the liver is the main place for complement synthesis (80% to 90% of the complement components in plasma are synthesized in hepatocytes), hepatic stellate cells, Kupffer cells, and hepatic sinusoidal epithelial cells all express C5a receptors. These objective conditions clarify the role of the complement system in liver diseases, this study is the first to propose a correlation between C5 gene polymorphism and HCC susceptibility. In the future, screening and follow-up can be carried out in high-risk populations under the premise of improving the correlation between C5 gene polymorphism and C5 serum concentration and the pathogenesis of C5a serum concentration and HCC, to accurately assess the risk of HCC in individuals, so as to reach the early stage of preventing HCC. Early detection and early treatment in the prevention and treatment of malignant tumors can significantly improve the patient's prognosis and quality of life. With the extensive use of genome-wide scanning technology, linkage analysis, family analysis and SNP as the third-generation genetic markers, we can gradually achieve early screening of malignant tumors or other diseases to obtain better clinical results. At present, C5a receptor blockers have been confirmed in experiments that can significantly slow down the progress of liver cirrhosis and reduce the content of collagen in liver cells. In addition, C5a-containing tumor vaccines can be used to inhibit tumor growth. Therefore, based on individualized early treatment considerations, if the C5 gene polymorphisms shown in the results of this study can be used as one of the basis, it may be more helpful for the development of related biological agents. The development of interrupted HCC helps to strengthen the prevention and treatment of HCC, further reduce the incidence of high-risk patients, reduce the mortality of HCC patients, and improve the prognosis of patients.
  11. A group of proteins that make up connective tissues and interstitial cells of animals are mainly collagen, elastin, and proteoglycans. Tissues and organs are formed by cell adhesion and connection of these three components. They not only have the functions of maintaining cell morphology, mechanical support and weight bearing, but also play a role in defense, protection, nutrition and repair. The initial process is to synthesize on the cytoplasmic ribosomes, and then enter the endoplasmic reticulum through the signal peptide sorting pathway to continue to synthesize, and some continue to synthesize in the cytoplasm. Generally, secreted proteins must go through the ER pathway through the Golgi It is secreted by the body, and the structural protein itself has a retention signal that will not be secreted and reaches the point of action through the intracellular transport pathway. British scientists wrote in the latest issue of the Proceedings of the National Academy of Sciences that they have discovered the origin of the protein structure responsible for the metabolism of Earth's life. These simple molecules provide power for the early life of the Earth and can serve as chemical signals for Teams such as NASA use it to find life on other planets. According to a report from the Physicists' Organization Network on the 16th, in the latest research, scientists at Rutgers University's "Evolution of Nanomachines in Geosphere and Microbial Ancestors" (ENIGMA) team traced the enzyme (protein) The evolutionary process found 3.5 to 2.5 billion years ago, the earliest two metabolic proteins in the evolution of life. The ENIGMA project aims to reveal the role of the simplest proteins that catalyze the earliest stages of life. In the latest study, the ENIGMA team studied two protein "folds": a ferredoxin fold that binds to iron-sulfur compounds, and a "Rossman" fold that binds to nucleotides (a component of DNA and RNA). They believe that these two folds are likely to be the earliest structures of early metabolism. Moreover, there is evidence that the two folds may have a common ancestor. If true, this ancestor may be the first metabolic enzyme in life on Earth. Researchers explain that proteins are amino acid chains, and the 3D path of amino acid chains in space is called folding. Ferredoxins are metals found in modern proteins that allow electrons to shuttle around cells to promote metabolism. Electrons flow through solids, liquids, and gases and power living systems. Other planetary systems must also have the same electricity in order for life to thrive. ENIGMA principal researcher Paul G. Folkovsky said: "We believe that life is made up of very small parts, which then make cells and eventually produce complex organisms like humans. Now we have found It is these building blocks that ultimately lead to the evolution of cells, animals and plants. " Research collaborator Vicas Nanda, a professor of biochemistry and molecular biology, said: "We know very little about how life originated on Earth, and the latest research allows us to understand and discover the earliest metabolic proteins. " It is reported that researchers will conduct tests in the laboratory to better understand the origin of life on Earth, and hope to observe how the life of other planets originated accordingly. Many proteins are important substances that make up the structure of cells and organisms, and are called structural proteins. For example, the components of feathers, muscles, hair, spider silk, etc. are mainly structural proteins.
  12. A 300 Watt LED grow light is a popular choice among many indoor gardeners for a number of reasons. These lights are available in sizes, styles, and shapes to fit just about any indoor garden. A LED panel is also a great choice for anyone interested in growing plants in large numbers. One of the benefits to choosing a 300 Watt LED light instead of a more conventional incandescent bulb is the fact that they produce very little heat and use only a fraction of the electricity of more traditional grow light choices. Heat is an important thing to keep in mind when purchasing a grow light. Because a 300 Watt LED grow light is very cool to the touch, there is no need for a gardener to worry about drying out the plants or causing drought like conditions. Incandescent bulbs actually produce more heat than light. When a light bulb creates heat, it is a sign of wasted energy. The truth is that incandescent light bulbs are the most inefficient lighting choice available on the market today. Even a fluorescent bulb is a better choice for energy conscious gardeners, although they are not as efficient as a LED panels. Another benefit to using a 300 Watt LED grow light is that, because of their low heat, they can actually be placed much closer to the plants. This is especially beneficial for plants that require intense light for long periods of time. A LED panel will also outlast just about any other type of light available on the market. In fact, LEDs have been shown to last five, 10, and even 15 years in certain applications. This means that a gardener does not have to be concerned about constantly replacing burned-out grow lights. A person should keep in mind, however, that a 300 Watt LED grow light is going to be considerably more expensive than some of the cheaper alternatives on the market. Their higher initial investment has put some budget conscious gardeners off of the idea of purchasing LED grow panels. While it is true that a person will have to pay more at first, they will more than make the money back in lower energy costs, fewer replacement purchases, and healthier plants overall. When an individual really thinks about it, a 300 Watt light really is a smart choice. Please keep this in mind when purchasing your lighting supplies.
  13. WHY HYDROPONICS? Hydroponics enable us to grow plants indoors with great results. A lot of plants will grow indoors with ease with just water as the feed however these will not produce large flowers or thickened foliage, simply adding a quality feeding schedule will spurn the plant on no end with just daylight from outdoors as the light signal. You can not regulate these plants cycles though because you can not change our weather and lighting times, this is where artificial light came into hydroponics in the first instance, to supply a constant light signal at timed intervals, regardless of the time of year. It was soon noted that these plants beneath 'hydroponics lighting' reacted to there natural growth pattern by the lights being on for 16 to 18 hours a day and if switched to 10-12 hours a day there flowering cycle was ignited. By pure accident fighting with the elements from the cold outside was it discovered that the stronger this light source the greater these plants growth rate was spoke volumes when it came to flowering. Of course light alone will not produce growth or flowering at high rates unless the air is full of Co2 and the feeding is of quality minerals and nutrients. GROWING PLANTS INDOORS And so 'Growing Plants Indoors' began. Followed by the odd Hydroponics retailer, to serve the community of course, however these retailers never wanted to share the science behind hydroponics as the harder it is for you to achieve what your mate can, (or the retailer), the more money you will spend trying. Then The World Wide Web ( www.) was discovered and hydroponics retailers fell out of the sky and growing plants indoors became common place. However the more 'spicy' variety of plant being the choice for many a youth bringing hydroponics into disrepute but what was discovered was that one of the fastest growing plants in the World could be grown indoors with ease resulting in unheard of yields along with the shear fact that these plants contain certain properties that help the medically sick. Further more as the years passed Supermarkets began to grow their own fruit, vegetables, flowers and herbs in great quantities due to the British weather being so uncertain, leaving our farmers hanging by threads. Today it is estimated that there are over 40,000 Hydroponics Farms, growing plants indoors to supply the Supermarket demands. Around 2.5 million Brits grow their own fruit and veg, some in gardens and allotments but the majority are growing indoors with better yields than those ever recorded growing outdoors. Tomatoes are by far the leader in the novice gardeners choice 'first grow', followed closely by Chillies. Both thrive growing indoors, infact in 26 years I have not found a plant that can not be grown in Hydroponics indoors. SO HOW DO WE DECIDE WHAT HYDROPONICS TO USE INDOORS? There are many methods firstly to ponder over, all done correctly will result the same but different methods can speed up the growth or vise versa the flowering, mastering which one works best for yourself is the answer but firstly understanding the methods science will make a better grower out of you resulting in untold yields. Once your method is chosen to suit yourself and your growing environment (grow room / grow tent / grow cabinet) the choice of system or Pot if using pot culture. To decide how many plants your going to grow you must first decide what strength of light you are going to use. One too strong for the grow room will resulting in too much heat and again vise versa too small may be too cold, one thing for sure is your room will change the amount of heat it uses and produces if it is hot or cold out side. This is where fan speed controllers, fans and carbon filters are required to maintain fresh Co2 is sourced and the old removed along with heat and some moisture. Before choosing your light ensure you are purchasing one to meet the targeted yield. It is a known fact that Fruit can only be flowered to match the light, gram per watt. i.e. 600 watt lamp produces 600 grams of dry, cured fruit or herbs. A choice of timed feeding is now simplified with the ever increasing range of cycle timers appearing on the market. With a good model bearing variations of timings from 15 seconds to 6 hours of feeding at intervals from 6 hourly to every 15 minutes the correct feeding schedule cam be maintained with great ease and satisfaction you know the plants are getting the feed without having to manually feed each plant, which could take you a long time if you had a large crop or two. The main factors left and the most important is the choice of fertiliser, minerals and nutrients you are to use. Of course not only do they have to be suited for the chosen method you are incorporating they have to suit the plant you are growing and the cycle the plant is in. (a) Grow feed is known as Vega or vegetation feed, (b) Flower feed is known as Flores or floral feed. Next you have to take into account each main stage of the plants life from start to finish with additives. This is not to be confused with the plants cycle. Root protection, your plants will require root protection in their early days to encourage roots to grow then secondly to keep these new roots healthy. Root nutrients and additives should be given until flowering. Many root additives can be added to the foliar feeding and used until flowering or fruiting starts. Vegetation Foliage, this is to be encouraged to flourish as the foliage is the plants main air intake routes. For this Nitrozymes are pre-added to the Vega feeds but also adding a separate additive of pure Nitrozymes will boost the foliage and growth rates immensely. For those using soils, Coco and such like substrates will benefit from also adding products such as Cannazyme which contain enzymes and minerals to repair the deadening roots and turn them into feed for the soils and plants.When the flowering cycle begins all feeds used in Vegetation is not used with exception to Cannazyme for those using soils, with hydro the roots are fed oxygen via an air pump pushing air into the nutrient reservior through air diffusers, this ensures the root zone is fed with oxygen and will keep the roots from dying and rotting. Continued use of root additives is highly beneficial. Flowering feeds are more complex in that each one has to be at critical timings to enable full yielding. Firstly Floral feed is required which will tell the plants recepticles to switch into flowering mode along with the change in lighting timings. All floral feeds contain the basics required to feed your plants the necessary minerals to flower successfully however plants really do need that extra push to reach high yields.Flower boosters are recommended and can be used from day one of flowering along with your floral feed to flourish growing plants indoors. Around weeks 4-6 your plants will now also require added Phosphurs and Pottasium (PK) on top of the booster and floral feed. Cannazymes are then required to repair the root zone from the harsh chemicals found in the Phosphurs and pottasium feeds (PK). This you add into the flower booster and floral feeding schedule thus ensuring the roots can uptake the water required to clean the plants substrates cleaning the minerals and nutrients telling the plant to finish its cycle. A supplement known as Flush is widely available and helps to (a), tell the plant to finish its flowering cycle (b), cleans the substrate, roots and stalks of existing feeds, and (c), Flush cleans out the plants of unwanted salts. Foliar feeding of flower boosters is highly recommended from day one of flowering until Flush has been applied. Not all flower boosters can be added to the plants using foliar feeding. WHERE TO SOURCE YOUR HYDROPONICS? Hydroponics and growing plants indoors is simple which is why so many people across the World are now taking part in growing their own produce, whatever that may be with the vast amount of options of variety of plants available to grow in either seed form or clones. We at Down The Road! Supplies Ltd take pride in offering hydroponics products, equipment and services. We are alone in the services we offer such as zero percent finance to help break the initial costs. Along with this, any persons wishing for their own grow room designed, built, hydroponics products supplied and installed, along with full feeding schedule then please contact us to arrange an appointment through our online store or phone 01926 632999. Hydroponics is a science that whilst simple to learn, will enthral you for years to come. The possibilities are endless using hydroponics equipment, anything that grow's in the wild can be grown using hydroponics cultivation methods, benefiting from speeding up the growth cycle of any plant species, offering the grower complete control over feeds, cycles, lighting and climate. Caring for those indoor plants has always been a challenge: even in well-lit rooms, many plants are not able to receive sufficient light to grow as fully as they would otherwise. LED Grow Lights with full spectrum are ideal for all kinds of Indoor Growing Plants veg and bloom at all growth stages. LED Grow Lights can also be used for large-scale cultivation of plants, crops, flowers, cannabis/marijuana and fruits. Home Grow Pro Shop specializes in LED Grow Lights for home-growers. We provide a memorable shopping experience by offering quality full spectrum LED Grow Lights with top-notch, prompt customer service.
  14. Types of antibiotics in milk a. β-lactams β-lactams include penicillins and cephalosporins, which are often used in the clinical treatment of dairy cattle and other livestock individuals and are left in the milk. Tetracyclines Common types of Tetracyclines have tetracycline, chlortetracycline, oxytetracycline, doxycycline, etc., which is a class of broad-spectrum antibiotics. Aminoglycosides Common types of Aminoglycosides include gentamicin, streptomycin, dihydrostreptomycin, neomycin, spectinomycin, etc., which are aminoglycoside antibiotics commonly used in livestock. Chloramphenicol Chloramphenicol includes the following three compounds: chloramphenicol, thiamphenicol, and florfenicol. These drugs are strictly restricted veterinary drugs, and some countries prohibit their use. Macrolides Common types of Macrolides are erythromycin, gentamicin, lincomycin, spiramycin and salinomycin. Sulfa Common types of Sulfa are sulfadiazine, sulfadimethoxine, sulfadiazine, sulfadiazine, etc. Trimethoprim is a sulfamethoxin synergist and is not used alone. The hazards of antibiotic residues Antibiotic residues have different degrees of harm to human health, ecological balance, dairy product prices and international trade in dairy products. The detection method of antibiotics in milk 1). Traditional microbiological testing method The microbiological detection method appeared earlier. Since its appearance, it has greatly improved the development of antibiotic detection methods. Its measurement principle is based on the antibiotics have a certain inhibitory effect on the physiological function and metabolism of microorganisms, which is consistent with clinical applications. It takes a long time and has a large rate of error. At present, the most commonly used methods are TTC method, Delvotest SP method, BY method, etc. 2). Internationally accepted testing methods Relatively speaking, it is an earlier universal measurement method applied in the world. Its principle is: if the milk contains antibiotics, add bacteria (Streptococcus thermophilus) and cultivate for 2.5-3h, adding the TTC indicator (triphenyltetrazolium) does not cause a reduction reaction, so the sample is colorless. If the milk contains no antibiotics, the sample is red. Relatively speaking, this method is relatively low-cost, but time-consuming, so its application is not too wide, and its development is subject to certain restrictions. 3). Blue and yellow detection method This method is a broad-spectrum microbial inhibition method, relatively speaking, it takes a short time, you can check the residue of antibiotics in a short time, as long as you can draw a conclusion by color comparison. As a result, there is a certain error rate for the detection obtained by this detection method, which is easy to cause false detection, but it is short in time and low in cost. 4). Modern instrumental analysis This method mainly uses modern instruments to detect and determine the type of antibiotics remaining. The most commonly used methods are chromatography, fluorescence, capillary electrophoresis, and chromatography-mass spectrometry. Use different theories and adopt different methods for testing, improve the standard of testing, and strengthen the quality of testing. Relatively speaking, this method has a fast separation speed, high efficiency, and automatic control. It can detect the specific content of antibiotics, and the results are more accurate. However, the sample to be tested needs a series of pretreatments, which is tedious and time-consuming, and must have the corresponding price. It is generally used in large laboratories, suitable for accurate determination. 5). Biochemical Immunity This has been gradually developed in recent years with the development of new technologies. It combines the specificity and reversibility of antigens and antibodies, and is an analytical technique. The basic principle is the competitive combination of antigens, which can be divided into enzyme-linked immunoassay (ELISA), fluorescent immunoassay (FIA), immunoassay technology and conventional physical and chemical analysis technology combined methods. Several methods have their own advantages and disadvantages, and we must pay attention to their comprehensive use to improve the quality and accuracy of detection. Judging from the results of its practice, it has a good detection effect on the current status of antibiotic residues, and its sensitivity is extremely high, reaching the level of ng; the detection is fast and specific. Relatively speaking, this method has a high degree of specificity, and each time an antibiotic is tested, a corresponding antigen or antibody must be prepared or purchased, resulting in a higher test cost. Therefore, the biochemical immunoassay cannot replace conventional analytical methods such as chromatography or spectroscopy, and can only serve as an important supplement. 6). Specific kits The so-called special kit method is based on the culture of agar medium containing Bacillus and PH indicator at a certain temperature, generally maintained at about 65 celsius, spore development and growth, reduce the pH value of the medium; under the action, the blue (purple) color becomes green-yellow. Antibiotic residues in raw milk inhibit the growth of microorganisms and the production of acids. Since no acid is produced, the color will not change.
  15. Somatic pluripotency reprogramming technology can transform differentiated somatic cells into induced pluripotent stem cells (iPSC) by using reprogramming transcription factors (mainly Oct4, Sox2 and Klf4). This technology was first published in 2006 by Professor Yamanaka and because of that, he won the Nobel Prize in Physiology or Medicine in 2012. However, the exact molecular mechanism involved in this technology is still to be studied. A recent research team led by Ralf Jauch, Vikas Malik and others has revealed the initial molecular mechanism of transcription factor-induced somatic pluripotency reprogramming and clarified the temporal dependence of pluripotency reprogramming on Oct4 and Sox2 for regeneration Medicine and research on induced pluripotent stem cells provide new theoretical models. The research results were published in the August 2 issue of Nature Communications. The Jauch team is focused on studying Oct4 and Sox2 transcription factors and how they play a leading role in the reprogramming process. After comparing the combination of wild-type and mutant Oct4 with Sox2 by using genomics technology, they were surprised to find that Sox2 instead of Oct4 is the key factor to turn on somatic cell reprogramming. In the initial stage of reprogramming, Sox2 “attacks” and “awakens” the so-called pluripotent genes in somatic cells, which is the primary condition for activating them. At this stage, Oct4 is not important for the inhibition of somatic characteristics, and plays an optional role. However, in order to finally open the relevant gene network to establish pluripotency, Sox2 and Oct4 work closely together to complete this work. In the later period of reprogramming, Oct4 gradually played a leading role. Once the cells become pluripotent stem cells, the dependence of the maintenance of pluripotency on the binding of Oct4 and Sox2 is greatly reduced. Since Oct6 binds to different genomic loci and lacks the bias of binding to Sox2, it cannot replace Oct4 for pluripotency reprogramming. These findings have answered some controversial issues in the field of pluripotency reprogramming research, and will provide directions for transforming Sox2, Oct4 and related factors to more quickly, efficiently and reliably perform cell reprogramming, and ultimately achieve clinical applications of stem cells and regenerative medicine. Original title: Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 Original source: https://www.nature.com/articles/s41467-019-11054-7